| 1. |
- Tofigh, Ali, et al.
(författare)
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A global structural em algorithm for a model of cancer progression
- 2011
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Ingår i: Adv. Neural Inf. Process. Syst.: Annu. Conf. Neural Inf. Process. Syst., NIPS. - : Neural Information Processing Systems.
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Konferensbidrag (refereegranskat)abstract
- Cancer has complex patterns of progression that include converging as well as diverging progressional pathways. Vogelstein's path model of colon cancer was a pioneering contribution to cancer research. Since then, several attempts have been made at obtaining mathematical models of cancer progression, devising learning algorithms, and applying these to cross-sectional data. Beerenwinkel et al. provided, what they coined, EM-like algorithms for Oncogenetic Trees (OTs) and mixtures of such. Given the small size of current and future data sets, it is important to minimize the number of parameters of a model. For this reason, we too focus on tree-based models and introduce Hidden-variable Oncogenetic Trees (HOTs). In contrast to OTs, HOTs allow for errors in the data and thereby provide more realistic modeling. We also design global structural EM algorithms for learning HOTs and mixtures of HOTs (HOT-mixtures). The algorithms are global in the sense that, during the M-step, they find a structure that yields a global maximum of the expected complete log-likelihood rather than merely one that improves it. The algorithm for single HOTs performs very well on reasonable-sized data sets, while that for HOT-mixtures requires data sets of sizes obtainable only with tomorrow's more cost-efficient technologies.
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| 2. |
- Zhou, Jing, et al.
(författare)
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Initial clustering - a key factor for phase separation kinetics in Fe-Cr-based alloys
- 2014
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Ingår i: Scripta Materialia. - : Elsevier BV. - 1359-6462 .- 1872-8456. ; 75, s. 62-65
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Tidskriftsartikel (refereegranskat)abstract
- Clustering of alloying elements in solution-treated Fe-Cr-based alloys is of considerable importance for their microstructure stability upon aging. The clustering of Cr after solution treatment in three stainless steel alloy categories has been studied by atom probe tomography. Furthermore, phase-field simulations are applied to examine the effect of initial clustering on phase separation evolution. It is concluded that the clustering of Cr found in solution-treated ferritic and duplex alloys plays a critical role in the nanostructure evolution during aging.
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| 3. |
- Cortazar-Chinarro, Maria, et al.
(författare)
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Major Histocompatibility Complex Variation and Haplotype Associated Survival in Response to Experimental Infection of Two Bd-GPL Strains Along a Latitudinal Gradient
- 2022
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Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media S.A.. - 2296-701X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- While both innate and adaptive immune system mechanisms have been implicated in resistance against the chytrid fungus Batrachochytrium dendrobatidis (Bd), studies on the role of specific MHC haplotypes on Bd infection are rare. Here, we studied variation in MHC Class IIB loci in the common toad Bufo bufo along a latitudinal gradient across Sweden. In general, Swedish toad populations had few MHC Class IIB haplotypes and MHC diversity declined from south (13 haplotypes) to the north (four haplotypes). The low diversity may compromise the ability of northern populations to fight emerging disease, such as Bd. In a laboratory experiment, we infected newly metamorphosed toads with two strains of the Global Pandemic Lineage of the fungus (Bd-GPL) and compared survival with sham controls. Bd-infected toads had lower survival compared to controls. Moreover, survival was dependent on the Bd-strain and northern toads had lower Bd-mediated survival than southern individuals. MHC diversity was lower in northern toads. All northern experimental animals were monomorphic for a single MHC haplotype, whereas we found seven different haplotypes in southern experimental animals. In southern toads, survival was dependent on both Bd-strain and MHC haplotype suggesting differential infection dynamics depending on both Bd-strain and host immune system characteristics.
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| 4. |
- Frigyesi, Attila, et al.
(författare)
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Independent component analysis reveals new and biologically significant structures in micro array data
- 2006
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: An alternative to standard approaches to uncover biologically meaningful structures in micro array data is to treat the data as a blind source separation ( BSS) problem. BSS attempts to separate a mixture of signals into their different sources and refers to the problem of recovering signals from several observed linear mixtures. In the context of micro array data, "sources" may correspond to specific cellular responses or to co-regulated genes. Results: We applied independent component analysis (ICA) to three different microarray data sets; two tumor data sets and one time series experiment. To obtain reliable components we used iterated ICA to estimate component centrotypes. We found that many of the low ranking components indeed may show a strong biological coherence and hence be of biological significance. Generally ICA achieved a higher resolution when compared with results based on correlated expression and a larger number of gene clusters with significantly enriched for gene ontology ( GO) categories. In addition, components characteristic for molecular subtypes and for tumors with specific chromosomal translocations were identified. ICA also identified more than one gene clusters significant for the same GO categories and hence disclosed a higher level of biological heterogeneity, even within coherent groups of genes. Conclusion: Although the ICA approach primarily detects hidden variables, these surfaced as highly correlated genes in time series data and in one instance in the tumor data. This further strengthens the biological relevance of latent variables detected by ICA.
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| 5. |
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| 6. |
- Höglund, Mattias, et al.
(författare)
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The origin of the Mendelian Society in Lund and the start of Hereditas.
- 2014
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Ingår i: Hereditas. - : Springer Science and Business Media LLC. - 1601-5223 .- 0018-0661. ; 151:6, s. 110-114
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Tidskriftsartikel (refereegranskat)abstract
- The Mendelian Society in Lund was founded in 1910. The initiative came from two young biologists supported by a wide circle of interested plant breeders and academics. Already from the start the society was dominated by the towering personality Herman Nilsson-Ehle. After two active years, the Society went into temporal hibernation until it resumed its activities in spring 1916, when Nilsson-Ehle was on his way to become Sweden's first professor of genetics. One of the aims of the Society was to launch a scientific journal for local scientists directed at an international audience. After a successful fundraising campaign, Hereditas was started in 1920. One of the original instigators of the Mendelian Society, Robert Larsson, became its first editor, and he remained in this position for more than 30 years. Both he and Nilsson-Ehle were fascinating personalities, deeply rooted in their time's scientific and ideological debates.
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| 7. |
- Lindgren, David, et al.
(författare)
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Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes
- 2017
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 20:6, s. 1476-1489
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Tidskriftsartikel (refereegranskat)abstract
- Comprehensive transcriptome studies of cancers often rely on corresponding normal tissue samples to serve as a transcriptional reference. In this study, we performed in-depth analyses of normal kidney tissue transcriptomes from the TCGA and demonstrate that the histological variability in cellularity, inherent in the kidney architecture, lead to considerable transcriptional differences between samples. This should be considered when comparing expression profiles of normal and cancerous kidney tissues. We exploited these differences to define renal-cell-specific gene signatures and used these as a framework to analyze renal cell carcinoma (RCC) ontogeny. Chromophobe RCCs express FOXI1-driven genes that define collecting duct intercalated cells, whereas HNF-regulated genes, specific for proximal tubule cells, are an integral part of clear cell and papillary RCC transcriptomes. These networks may be used as a framework for understanding the interplay between genomic changes in RCC subtypes and the lineage-defining regulatory machinery of their non-neoplastic counterparts.
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| 8. |
- Martijn, H., et al.
(författare)
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Development of IR imaging at IRnova
- 2009
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Ingår i: Infrared Technology and Applications XXXV. - : SPIE.
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Konferensbidrag (refereegranskat)abstract
- Historically IRnova has exclusively been a company, focused on manufacturing of QWIP detectors. Nowadays, besides continuous improvements of the performance of QWIP FPAs and development of new formats IRnova is involved in development of QWIP detectors for special applications and has started the development of the next generation infrared detectors, as well. In the light of the development of new formats we validate experimentally theoretical calculations of the response of QWIPs for smaller pixel size. These results allow for the development of high performance megapixel QWIP FPA that exhibit the high uniformity and operability QWIP detectors are known for. QWIP is also being considered for space applications. The requirements on dark current and operating temperature are however much more stringent as compared to the terrestrial applications. We show ways to improve the material quality with as a result a higher detector operating temperature. IRnova is also looking at antimony-based strained superlattice material for the LWIR region together with partners at theIMAGIC centre of excellence. One of the ways to overcome the problem with surface currents is passivating overgrowth. We will report the status and results of overgrowing the detector mesas with AlGa(As)Sb in a MOVPE system. At the same centre of excellence a novel material concept is being developed for LWIR detection. This new material contains a superlattice of vertically aligned and electronically coupled InAs and GaSb quantum dots. Simulations show that it should be possible to have LWIR detection in this material. We will present the current status and report results in this research.
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| 9. |
- Medved, Dennis, et al.
(författare)
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Improving prediction of heart transplantation outcome using deep learning techniques
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; :8
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Tidskriftsartikel (refereegranskat)abstract
- The primary objective of this study is to compare the accuracy of two risk models, International Heart Transplantation Survival Algorithm (IHTSA), developed using deep learning technique, and Index for Mortality Prediction After Cardiac Transplantation (IMPACT), to predict survival after heart transplantation. Data from adult heart transplanted patients between January 1997 to December 2011 were collected from the UNOS registry. The study included 27,860 heart transplantations, corresponding to 27,705 patients. The study cohorts were divided into patients transplanted before 2009 (derivation cohort) and from 2009 (test cohort). The receiver operating characteristic (ROC) values, for the validation cohort, computed for one-year mortality, were 0.654 (95% CI: 0.629–0.679) for IHTSA and 0.608 (0.583–0.634) for the IMPACT model. The discrimination reached a C-index for long-term survival of 0.627 (0.608–0.646) for IHTSA, compared with 0.584 (0.564–0.605) for the IMPACT model. These figures correspond to an error reduction of 12% for ROC and 10% for C-index by using deep learning technique. The predicted one-year mortality rates for were 12% and 22% for IHTSA and IMPACT, respectively, versus an actual mortality rate of 10%. The IHTSA model showed superior discriminatory power to predict one-year mortality and survival over time after heart transplantation compared to the IMPACT model.
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| 10. |
- Meurling, Sara, et al.
(författare)
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Body size mediates latitudinal population differences in response to Bd infection in two amphibian species
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The chytrid fungus Batrachochytrium dendrobatidis (Bd), is a generalist pathogen which has caused amphibian population declines worldwide. In many species Bd infection causes the disease chytridiomycosis, leading to high mortality. However, infection may cause sub-lethal fitness effects even in species that are resistant or tolerant to Bd. Moreover, populations of the same species may differ in their sensitivity to Bd, but the factors behind this variation are poorly understood. Here we exposed two common North European amphibians (moor frog Rana arvalis, common toad Bufo bufo) from two latitudinally divergent regions to two different BdGPL strains in a laboratory experiment. We found that Bd exposure lowered survival in both species, but this effect was much stronger in B. bufo. Moreover, survival was lower in the northern region in both species, this difference again being much stronger in B. bufo. Northern individuals were smaller in both species and the survival difference between regions was size mediated with smaller individuals being more sensitive to Bd. We discuss potential additional factors contributing to this result. Bd exposure also led to sub-lethal effects in terms of reduced growth in both species suggesting that even individuals surviving the infection may have reduced fitness mediated by reduction if body size. However, we did not detect any differences in amphibian responses to the two Bd strains.
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